Dr. Oliver Smithies, 2007 Nobel Prize winner and expert “tinkerer”, is best known for developing methods to genetically modify individual mammalian genes. This technique has had an enormous impact on biomedical research enabling advances in the understanding of genetic causes of diseases. In diabetes research, his group has used this technology to uncover a mechanistic link between genetic variants and diabetic predisposition to kidney disease. Beyond this, his natural propensity for invention and toolmaking has led to several notable scientific achievements.

Smithies was born in 1925 in Halifax, England, where his father was an insurance salesman and his mother taught English at the Halifax Technical College. At a young age, a bout with “rheumatic fever” resulted in a heart murmur, a condition that was considered serious at the time. This condition prevented him from participating in competitive sports for many years, fortuitously compelling him to enjoy reading and making things. He adapted an enthusiasm for building things from parts others had deemed useless. Later in life, his colleagues recognized this adeptness for refurbishing damaged or obsolete objects and often labeled them as NBGBOKFO: no bloody good, but OK for Oliver.

His aptitude for math landed him a scholarship to Balliol College, Oxford, where he began studying medicine. In his third year, he attended weekly tutorials taught by Professor Alexander G. Ogston, whose passion for biochemistry motivated Smithies to drop out of medical school and pursue research. His thesis work reinforced his “natural inclination to pursue experiments to conclusion with little regard for the time required” and launched his scientific career.

He continued his education as a postdoctoral fellow under Dr. Jack Williams at the University of Wisconsin and then was hired as a research chemist at the Connaught Medical Research Laboratories at the University of Toronto, the birthplace of insulin. Early on, insulin was extracted from animal sources and was commonly contaminated with another protein, now known as proinsulin. It was here, under Dr. David A. Scott, that Smithies attempted to find this then unknown factor. He turned to a method that uses electricity to separate proteins on filter paper. However, he soon discovered that insulin kept getting stuck to the paper. Summoning memories from his childhood of the starch his mother used for his father’s shirts turning to jelly when cooled, he developed the first ‘gel electrophoresis’ system. While his search for proinsulin was unsuccessful, this system enabled the discovery of new proteins in plasma that had not been previously seen by other researchers.

Shifting his interests towards genetics, Smithies eventually established himself at the University of North Carolina, where he became a Distinguished Professor of Pathology and Laboratory Medicine. His Nobel-prizewinning work sprouted from his interest in sickle-cell disease, where he harnessed gene-editing technology to replace the gene responsible for this disease with a normal gene. Until his passing in 2017, Smithies remained endlessly enthused about life at the bench and continued to come to the lab to “play”, claiming he never ‘worked’ a day in his life.

— Written by Nicole Revie